Summary of Work: Xenobiotics/steroid metabolizing enzymes, cytochromes P450 and sulfotransferases exhibit remarkably diverse substrate and product specificities. In an attempt to provide the structural insight into understanding these broad specificities, we have solved the crystal structure of mouse estrogen sulfotransferase-inactive cofactor PAP complex at 2.5A and the structure with PAP and estradiol at 2.7A. The overall fold is similar to nucleotide kinases, that indicates the evolutionary and mechanistic resemblances between sulfonation and phosphorylation. The substrate is buried in a hydrophobic creft. The structural motif named PSB-loop is identified as the binding site for the 5'-phosphosulfate of the active cofactor PAPS. The PSB-loop is apparently conserved in various sulfotransferases including bacterial, insect and plant sulfotransferases. Characteristically, the P450 genes are induced by xenobiotics as a cellular defense mechanism against the toxicity and carcinogenicity of the xenobiotics. During the induction, the P450 CYP2B gene transcriptionally activated by the vast variety of structurally unrelated xenochemicals. Using the primary hepatocytes developed by this section, the 51-bp universal DNA enhancer designated PBREM of this P450 gene is identified. PBREM that responds to the extremely diverse xenochemicals is a composite element that contains two nuclear factor-binding sites and NF1 binding site. These xenochemicals include phenobarbital, some xenoestrogens (e.g. o,p'-DDT, methoxchior), polychlorinated biphenyls, organic solvents (e.g. acetone, pyridine) and drugs such as clotimazole and chlorpromazine.